The continuing goal of this project is to gain quantitative information on the number, the nature, and the acute response to ionizing radiation of the cells involved in the neoplastic process in the rat mammary gland following irradiation, and to relate these effects to the late appearance of radiogenic neoplasms. Our hypothesis is that radiogenic carcinomas are derived from that cell population which is essential to tissue repair and repopulation following radiation damage. We have developed quantitative mammary cell transplantation techniques which are being applied to investigate the effects of physical factors as, for example, radiation type, and biological factors such as the role of hormonally controlled proliferation and differentiation, on cell survival, post-irradiation repair and neoplasia. Our ultimate goal is to define the mammary carcinoma risk per rad per surviving clonogenic cell under defined physiologic circumstances. We believe the results will contribute directly to an understanding of radiation carcinogenesis in general and breast cancer in particular. The latter is the foremost malignant disease of American women and a major cause of morbidity and mortality among those exposed to ionizing radiation. Our specific aims during the proposed grant period shall be to concentrate and characterize the rat mammary cells which are clonogenic on transplantation and hormonal stimulation, and those cells which give rise to radiation-induced carcinomas.